Exosome secretion promotes chemotaxis of cancer cells
Exosome secretion promotes chemotaxis of cancer cells
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DOI：
10.1080/19336918.2016.1273307
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发表时间：
2017-01-01
影响因子：
3.2
通讯作者：
Weaver, Alissa M.
中科院分区：
文献类型：
--
作者：
Sung, Bong Hwan;Weaver, Alissa M.
细胞向化学信号或趋化作用的迁移，对于免疫防御、伤口愈合和癌症转移等许多生物过程都是重要的。尽管趋化性被认为发生在癌细胞中，但它的特征不如中性粒细胞等专业免疫细胞的趋化性。在这里，我们表明癌细胞的趋化性依赖于外切体型细胞外小泡的分泌。纤维肉瘤细胞向外切体耗尽血清的梯度迁移被外切体分泌调节因子Rab27a击倒而减少。在趋化小室中涂有纯化的胞外小泡的救援实验表明，外切体而不是微囊影响细胞迁移的速度和方向性。用纯化的纤维连接蛋白和去除纤维连接蛋白的外切体包被的小室表明，外切体运输的纤维连接蛋白促进了细胞的速度，但不能解释外切体在促进纤维肉瘤细胞在趋化过程中运动的方向性的作用。这些实验表明，外切体包含多个促进运动的货物，这些货物对细胞运动的不同方面有贡献。
Migration of cells toward chemical cues, or chemotaxis, is important for many biologic processes such as immune defense, wound healing and cancer metastasis. Although chemotaxis is thought to occur in cancer cells, it is less well characterized than chemotaxis of professional immune cells such as neutrophils. Here, we show that cancer cell chemotaxis relies on secretion of exosome-type extracellular vesicles. Migration of fibrosarcoma cells toward a gradient of exosome-depleted serum was diminished by knockdown of the exosome secretion regulator Rab27a. Rescue experiments in which chemotaxis chambers were coated with purified extracellular vesicles demonstrate that exosomes but not microvesicles affect both speed and directionality of migrating cells. Chamber coating with purified fibronectin and fibronectin-depleted exosomes demonstrates that the exosome cargo fibronectin promotes cell speed but cannot account for the role of exosomes in promoting directionality of fibrosarcoma cell movement during chemotaxis. These experiments indicate that exosomes contain multiple motility-promoting cargoes that contribute to different aspects of cell motility.